YIPF6 is a five transmembrane-spanning protein localized to the Golgi apparatus that plays critical roles in vesicular transport and tissue homeostasis 1. The protein exhibits a broad distribution throughout the Golgi stack, with a cytosolic N-terminal domain and five closely stacked transmembrane domains 2. YIPF6 functions in multiple transport pathways: it controls the sorting and secretion of FGF21 by binding to it in the endoplasmic reticulum and regulating its packaging into COPII vesicles 3, and it interacts with TVP23B to maintain proper Golgi proteome composition, particularly glycosylation enzymes 4. Loss of YIPF6 function has significant pathological consequences. Yipf6-null mice develop spontaneous intestinal inflammation and extreme sensitivity to colitis, attributed to defective formation and secretion of large secretory granules from Paneth and goblet cells 1. This leads to compromised intestinal barrier function with decreased antimicrobial peptides and increased mucus permeability 4. Clinically, YIPF6 levels in human liver correlate with hepatic steatosis and inversely with serum FGF21 in NAFLD patients 3. YIPF6 has also been identified as a potential biomarker, showing altered expression in acute myeloid leukemia prognosis models and Machado-Joseph disease 56.